Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-11-03
2000-04-04
Davis, Zinna Northington
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546146, C07D21704, A61K 3147
Patent
active
060462108
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel tetrahydroisoquinoline derivatives, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D.sub.3 receptors, in particular as antipsychotic agents.
U.S. Pat. No. 5,294,621 describes tetrahydropyridine derivatives of the formula: ##STR2## wherein ##STR3## is an optionally substituted thienyl or optionally substituted phenyl ring; R.sup.1, R.sup.2 and R.sup.3 are each inter alia hydrogen; X is inter alia (CH.sub.2)mNR.sup.7 CO; m is 2-4; and Ar.sup.1 is an optionally substituted heterocyclic ring or an optionally substituted phenyl ring. The compounds arm said to be useful as antiarrhythmic agents.
We have now found a class of tetrahydroisquinoline derivatives which have affinity for dopamine receptors, in particular the D.sub.3 receptor, and thus potential in the treatment of conditions wherein modulation of the D.sub.3 receptor is beneficial, eg as antipsychotic agents.
In a first aspect the present invention provides compounds of formula (I): ##STR4## wherein: R.sup.1 represents a substituent selected from: a hydrogen or halogen atom; a hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethanesulfonyloxy, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, arylC.sub.1-4 alkoxy, C.sub.1-4 alkylthio, C.sub.1-4 alkoxyC.sub.1-4 alkyl, C.sub.3-6 cycloalkylC.sub.1-4 alkoxy, C.sub.1-4 alkanoyl, C.sub.1-4 alkoxycarbonyl, C.sub.1-4 alkylsulphonyl, C.sub.1-4 alkylsulphonyloxy, C.sub.1-4 alkylsulphonylC.sub.1-4 alkyl, arylsulphonyl, arylsulphonyloxy, arylsulphonylC.sub.1-4 alkyl, C.sub.1-4 alkylsulphonamido, C.sub.1-4 alkylamido, C.sub.1-4 alkylsulphonamidoC.sub.1-4 alkyl, C.sub.1-4 alkylamidoC.sub.1-4 alkyl, arylsulphonamido, arylcarboxamido, arylsulphonamidoC.sub.1-4 alkyl, arylcarboxamidoC.sub.1-4 alkyl, aroyl, aroylC.sub.1-4 alkyl, or arylC.sub.1-4 alkanoyl group; a group R.sup.3 OCO(CH.sub.2).sub.p, R.sup.3 CON(R.sup.4)(CH.sub.2).sub.p, R.sup.3 R.sup.4 NCO(CH.sub.2).sub.p or R.sup.3 R.sup.4 NSO.sub.2 (CH.sub.2).sub.p where each of R.sup.3 and R.sup.4 independently represents a hydrogen atom or a C.sub.1-4 alkyl group or R.sup.3 R.sup.4 forms part of a C.sub.3-6 azacyloalkane or C.sub.3-6 (2-oxo)azacycloalkane ring and p represents zero or an integer from 1 to 4; or a group Ar.sup.2 --Z, wherein Ar.sup.2 represents an optionally substituted phenyl ring or an optionally substitted 5- or 6-membered aromatic heterocyclic ring and Z represents a bond, O, S, or CH.sub.2 ; phenyl ring or an optionally substituted 5- or 6-membered aromatic heterocyclic ring; and --(CH.sub.2).sub.m Y.sup.1 (CH.sub.2).sub.n --, wherein Y.sup.1 represents O, S, SO.sub.2, or CO and m and n each represent zero or 1 such that the sum of m+n is zero or 1;
In the compounds of formula (I) above an alkyl group or moiety may be straight or branched. Alkyl groups which may be employed include methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl and any branched isomers thereof such as isopropyl, t-butyl, sec-pentyl, and the like.
When R.sup.1 represents an arylC.sub.1-4 alkoxy, arylsulphonyl, arylsulphonyloxy, arylsulphonylC.sub.1-4 alkyl, arylsulphonamido, arylcarboxamido, arylsulphonamidoC.sub.1-4 alkyl, arylcarboxamidoC.sub.1-4 alkyl, aroyl, aroylC.sub.1-4 alkyl, or arylC.sub.1-4 alkanoyl group, the aryl moiety may be selected from an optionally substituted phenyl ring or an optionally substituted 5- or 6-membered heterocyclic ring. In the group R.sup.1 an aryl moiety may be optionally substitued by one or more substituents selected from hydrogen, halogen, amino, cyano, C.sub.1-4 alkyl, C.sub.1-4 alkylamino, C.sub.1-4 dialkylamino, C.sub.1-4 alkylamido, C.sub.1-4 alkanoyl, or R.sup.5 R.sup.6 NCO where each of R.sup.5 and R.sup.6 independently represents a hydrogen atom or C.sub.1-4 alkyl group.
A halogen atom present in the compounds of formula (I) may be fluorine, chlorine, bromine or iodine.
When q is 2, the substituents R.sup.1 may be the same or different. Preferably q represents 1.
An optionally substituted 5- or 6-membered hete
REFERENCES:
patent: 5294621 (1994-03-01), Russell
Johns Amanda
Stemp Geoffrey
Davis Zinna Northington
Kinzig Charles M.
SmithKline Beecham p.l.c.
Stein-Fernandez Nora
Williams Janice E.
LandOfFree
Tetrahydroisoquinoline derivatives as modulators of dopamine D.s does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Tetrahydroisoquinoline derivatives as modulators of dopamine D.s, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Tetrahydroisoquinoline derivatives as modulators of dopamine D.s will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-365561